Objective: This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of intramuscular (IM) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or schizo-phreniform disorder.
Method: Patients were randomly assigned to IM aripiprazole 1 mg, 5.25 mg, 9.75 mg, or 15 mg; IM haloperidol 7.5 mg; or placebo and observed for 24 hours. The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component (PEC) score from baseline to 2 hours after initial dosing. Secondary measures included the Agitation-Calmness Evaluation Scale (ACES) score. The study was carried out at 50 centers worldwide between April 2002 and January 2003.
Results: A total of 357 patients were randomly assigned to treatment. Intramuscular aripiprazole 5.25 mg, 9.75 mg, and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo. These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group, with a trend toward significance (p = .051) at 30 minutes. Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes. At 30 minutes, significantly more patients responded (defined as a greater than or equal to 40% reduction in PEC score) to IM aripiprazole 9.75 mg versus placebo (27% vs. 13%, p = .05). Intramuscular aripiprazole 9.75 mg significantly improved agitation, without oversedation, as measured by change in ACES score from baseline to 2 hours versus placebo (p = .003). No patient discontinued the study because of treatment-emergent adverse events. Extrapyramidal symptoms occurred most frequently in the IM haloperidol group. The most common adverse event in IM aripiprazole recipients was headache.
Conclusion: Intramuscular aripiprazole 9.75 mg is a rapidly effective and well-tolerated alternative to IM haloperidol for the control of agitation, without oversedation, in patients with schizophrenia, schizo-affective disorder, or schizophreniform disorder.
Clinical trials registration: ClinicalTrials.gov identifier NCT00036127.